Recurrent mild cerebral ischemia: enhanced brain injury following acute compared to subacute recurrence in the rat

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dc.contributor.authorTuor, Ursula I.
dc.contributor.authorZhao, Zonghang
dc.contributor.authorBarber, Philip
dc.contributor.authorQiao, Min
dc.date.accessioned2016-05-27T18:17:33Z
dc.date.available2016-05-27T18:17:33Z
dc.date.issued2016-05-26
dc.descriptionPublisher's version of article deposited according to BioMed Central license agreement http://www.biomedcentral.com/authors/license May 27, 2016.en_US
dc.description.abstractBackground In the current study, a transient cerebral ischemia producing selective cell death was designated a mild ischemic insult. A comparable insult in humans is a transient ischemic attack (TIA) that is associated with functional recovery but can have imaging evidence of minor ischemic damage including cerebral atrophy. A TIA also predicts a high risk for early recurrence of a stroke or TIA and thus multiple ischemic insults are not uncommon. Not well understood is what the effect of differing recovery times between mild ischemic insults has on their pathophysiology. We investigated whether cumulative brain damage would differ if recurrence of a mild ischemic insult occurred at 1 or 3 days after a first insult. Results A transient episode of middle cerebral artery occlusion via microclip was produced to elicit mild ischemic changes—predominantly scattered necrosis. This was followed 1 or 3 days later by a repeat of the same insult. Brain damage assessed histologically 7 days later was substantially greater in the 1 day recurrent group than the 3 days recurrent group, with areas of damage consisting predominantly of regions of incomplete infarction and pannecrosis in the 1 day group but predominantly regions of selective necrosis and smaller areas of incomplete infarction in the 3 days group (P < 0.05). Enhanced injury was reflected by greater number of cells staining for macrophages/microglia with ED1 and greater alterations in GFAP staining of reactive astrocytes in the 1 day than 3 days recurrent groups. The differential susceptibility to injury did not correspond to higher levels of injurious factors present at the time of the second insult such as BBB disruption or increased cytokines (tumor necrosis factor). Microglial activation, with potential for some beneficial effects, appeared greater at 3 days than 1 day. Also blood analysis demonstrated changes that included an acute increase in granulocytes and decrease in platelets at 1 day compared to 3 days post transient ischemia. Conclusions Dynamic changes in multiple inflammatory responses likely contribute to the time dependence of the extent of damage produced by recurrent mild ischemic insults. The time of mild stroke recurrence is crucial with early recurrence producing greater damage than subacute recurrence and this supports urgency for determining and implementing optimal stroke management directly after a TIA.en_US
dc.description.grantingagencyCanadian Institutes for Health Researchen_US
dc.description.refereedYesen_US
dc.identifier.citationTuor UI, Zhao Z, Barber P, Qiao M. (2016). Recurrent mild cerebral ischemia: enhanced brain injury following acute compared to subacute recurrence in the rat. BMC Neuroscience, 17(28), 1-14. doi: 10.1186/s12868-016-0263-xen_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/33754
dc.identifier.grantnumberMOP111037en_US
dc.identifier.urihttp://hdl.handle.net/1880/51246
dc.language.isoenen_US
dc.publisherBiomed Central Ltd.en_US
dc.publisher.corporateUniversity of Calgary
dc.publisher.departmentDepartment of Clinical Neurosciences, Department of Physiology and Pharmacologyen_US
dc.publisher.facultyMedicineen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.urlhttp://bmcneurosci.biomedcentral.com/articles/10.1186/s12868-016-0263-xen_US
dc.rightsAn error occurred on the license name.*
dc.rights.uriAn error occurred getting the license - uri.*
dc.subjectCerebral ischemiaen_US
dc.subjectTransient ischemic attacken_US
dc.subjectStrokeen_US
dc.subjectRecurrenceen_US
dc.subjectInflammationen_US
dc.subjectGranulocytesen_US
dc.titleRecurrent mild cerebral ischemia: enhanced brain injury following acute compared to subacute recurrence in the raten_US
dc.typejournal article
thesis.degree.disciplinePhysiology
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